beta-NGF dimer binds to TrkA receptor

Stable Identifier
R-HSA-166542
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Neurotrophin dimer binding to TRK receptors causes receptor dimerization. Although the dissociation constants of NGF for TRK and p75NTR are very similar, the binding kinetics are quite different: NGF associates with and dissociates from p75NTR much more rapidly than from TRKA. p75NTR regulates the affinity and specificity of TRK receptor activation by neurotrophins is regulated. Its presence is required to observe high affinity binding to TRK receptors, since it increases the rate of neurotrophin association with TRK proteins. The major ligand binding domain in TRK receptors is the membrane-proximal Ig-C2-like domain (named Ig2 domain or domain 5), although other regions in in the TRK extracellular domains are also important for ligand binding.
The N termini of neurotrophins are important in controlling binding specificity, and the structure of this region is reorganized upon binding to a TRK receptor. In some neurons, TRK receptors are localized to intracellular vesicles in the absence of signals. Electrical activity, cAMP, and Ca2+ stimulate TRK insertion into the cell surface by exocytosis of cytoplasmic membrane vesicles containing TRK. At axon terminals, TRK receptors undergo ligand-dependent endocytosis upon ligand binding. The internalized neurotrophin-TRK complex is then sorted and enters either recycling or retrograde transport pathways.

Literature References
PubMed ID Title Journal Year
1850549 The trk proto-oncogene product: a signal transducing receptor for nerve growth factor

Kaplan, DR, Hempstead, BL, Martin-Zanca, D, Chao, MV, Parada, LF

Science 1991
10490030 Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor

Wiesmann, C, Ultsch, MH, Bass, SH, de Vos, AM

Nature 1999
1849459 The trk proto-oncogene encodes a receptor for nerve growth factor

Klein, R, Jing, SQ, Nanduri, V, O'Rourke, E, Barbacid, M

Cell 1991
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